Carnitine (vitamin Bt; 3-hydroxy-4-trimethylammonio-butanoate) is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is used as a nutritional supplement.
Carnitine exists in two stereoisomers. The biologically active form is L-carnitine, whilst its enantiomer, D-carnitine, is biologically inactive. When producing L-carnitine in an industrial process, it is desirable to produce the biologically active L-form in high purity. Highly pure L-carnitine can be obtained by microbiological processes. EP 0195944 discloses a microbiological process, in which L-carnitine is produced from crotonobetain and butyrobetain in a bioreactor with the aid of specific microorganisms. A mixture of enantiomeric pure L-carnitine with butyrobetain is obtained. In order to remove the butyrobetain, the final product is recrystallized with methanol and isobutanol.
Another microbiological process for obtaining essentially pure L-carnitine is disclosed by DD 296702. The culturing solution is depleted of L-carnitine by electrodialysis and recrystallization of the L-carnitine. In such microbiological processes, essentially no D-carnitine is produced and thus an enantiomeric separation step is not necessary. A recrystallization of L-carnitine from solvents is applied for removing other substances.
Obtaining highly pure L-carnitine is more complicated when using a non-microbiological or non-enzymatic process. By means of organic synthesis, usually a mixture of D- and L-carnitine is obtained. In order to obtain pure L-carnitine, DE 689 01 889 T2 suggests to apply a ruthenium phosphine complex in a stereoselective asymmetric hydrogenization. Such complexes are relatively complicated and expensive and thus not applicable for the preparation of large amounts of L-carnitine in an industrial process.
Thus methods have been developed for isolating L-carnitine from a mixture of L- and D-carnitine. In general, the methods are based on the conversion of carnitine into a salt with an optically active acid and separation of L- and D-carnitine due to different physical properties, such as solubility.
In this respect, DD 93 347 discloses a method for separating D- and L-carnitine in the presence of camphoric acid, dibenzoyl tartric acid or combinations thereof from alcoholic solutions. The D-carnitine is separated from the L-carnitine due to the different solubility of the salts.
DE 35 36 093 discloses a method for the preparation of L-carnitine from a racemic mixture, in which the D- and L-carnitine are converted to optically active salts with dibenzoyl-L-tartric acid followed by a fractionated crystallization.
However, methods in which the carnitine is converted into an optically active salt or acid are relatively complicated, because they comprise the steps of adding a separating agent and removing it after the separation process. This renders the overall process relatively time- and labour-efficient.